During Drosophila development the genomic DNA content is altered in many tissues as a consequence of changes in the coordination of cell cycle events. Endoreduplication, duplication of the genome without nuclear division and cytokinesis, produces polyploid cells in which the total genomic content has increased. In some tissues specific genomic regions are under or overreplicated as a result of an uncoupling of DNA replication origin usage from the cell cycle. The regulation of these two variations in the cell cycle is investigated in the proposed experiments. The genetic control of the endocycle will be analyzed by obtaining mutants affecting the switch to endoreduplication by the larval precursor cells during embryogenesis. These mutants will be isolated from an embryonic lethal collection generated by single- element transposon tagging. Three reagents that are differential markers for cell and nuclear size will be used to identify mutants causing polyploid cells to remain diploid or diploid cells to become polyploid in the embryo. The mutants in this collection can be readily mapped and cloned, thus permitting their molecular role in regulating developmental changes in the cell cycle to be elucidated. Two gene clusters encoding the chorion genes are overreplicated in the differentiation of the follicle cells. The amplification of these two chromosomal domains will be used as a model for analyzing differential replication. Characterization of the control elements regulating chorion amplification in cis has indicated that a common control element may function in regulating both replication and transcription. This will be tested in a series of experiments testing the linkage of the transcriptional control clement to the amplification control element, the effect of other transcriptional regulatory elements on amplification, and the replicative properties of the control region in cultured cells and embryos.